HCID 67098757, compound → HCID 136121409, compound

HRID 2079299Notes

Reaction equation

HRID 2079299 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1.C(O)(=O)C(O)=O.[OH:26][C@H:27]([CH2:36][CH:37]([CH3:39])[CH3:38])[C:28]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)=[O:29]>C(Cl)Cl>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[OH:19])[N:3]=[C:2]2[N:33]1[CH2:32][CH2:31][N:30]([C:28](=[O:29])[C@H:27]([OH:26])[CH2:36][CH:37]([CH3:38])[CH3:39])[CH2:35][CH2:34]1

Participants

4

Reactant 2

HCID 67098757HCID 67098757, compoundHCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

HCID 136121409HCID 136121409, compoundYield 91.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (200 mg, 0.72 mmol) and CH2Cl2 (7 mL) was added (R)-2-hydroxy-4-methyl-1-(piperazin-1-yl)pentan-1-one oxalate (275 mg, 0.95 mmol). The reaction was complete after two hours. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 mixture of CH2Cl2:hexanes gave (R)-1-(4-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one (289 mg, 91%). LC/MS: m/z 439.30 (M+H)+ at 3.00 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) d 8.46 (m, 1H), 8.02 (m, 1H), 7.84 (m, 2H), 7.40 (m, 1H), 6.97 (m, 2H), 4.92 (d, J=7.2 Hz, 1H), 4.38 (m, 1H), 3.98 (m, 4H), 3.76 (m, 4H), 1.80 (m, 1H), 1.42 (m, 2H), 0.92 (q, J=3.8 Hz, 6H) ppm.

Workup

  1. customPurification via silica gel chromatography
  2. additionin 50:50 mixture of CH2Cl2

Sources & evidence

ORD record
ord-318f8115c1e44f9e95e3799ebe56468e
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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